July 1, 2005

Dear Members of the Scientific and Medical Accountability Standards Working Group:

Congratulations on your appointment to the CIRM Standards Working Group. As you well know, you face the major responsibility of developing standards for cell and tissue extraction, research, clinical trials, and therapy delivery. These will have an impact beyond determining the ethical, socioeconomic, and financial boundaries for the research: The support of the public depends on their understanding that research using public tax dollars is conducted with the highest degree of integrity and transparency.

The Center for Genetics and Society and the Pro-Choice Alliance for Responsible Research support embryonic stem cell research, but are concerned about its potential for abuse and unintended consequences. We are mindful, as we know you are too, of the unacceptable price paid by racial and ethnic minorities, women, the disabled, and other vulnerable groups in past scientific endeavors. Having looked at the case of gene therapy, we believe that strong enforceable guidelines are in the best interests of medical research because they prevent situations that may undermine support for it.

In addition, we are concerned that unless properly regulated, stem cell research may open the door to human reproductive cloning and inheritable genetic engineering. Although funding for reproductive cloning is prohibited by Proposition 71, and is illegal in California and 10 other states, we do not yet have laws in place in the remaining 39 states or at the national level.

As you know, the CIRM leadership has provisionally adopted the recommendations developed by a committee of the National Academies as interim research guidelines. We are encouraged that many areas of concern are addressed in those guidelines, and in the questions posed by Alta Charo at the ICOC meeting of March 1 of this year. Because you are scheduled to discuss the National Academies guidelines at your July 6 meeting, we are here briefly summarizing some key points that we believe remain inadequately considered. We look forward to constructive dialogue about them.

The need for a central, independent oversight: The local "Embryonic Stem Cell Research Oversight" (ESCRO) committees that the National Academies report recommends are an inadequate substitute for a central oversight and regulatory mechanism -- fully independent of the ICOC -- for this research. Though the National Academies guidelines recommend that the ESCRO committees have public members, the committees as they are envisioned in the guidelines, like local Institutional Review Boards, will likely be weighted toward members close to the institutions -- public, private, and for-profit -- that will be involved the research.

We understand that in addition to the ESCROs, many institutions receiving funding from the CIRM will have either institutional IRBs or a similar body. We are concerned that members of ESCRO committees and IRBs may find it difficult to inconvenience their colleagues who wish to proceed with their projects, as has sometimes been the case with other kinds of biomedical research.

By way of contrast, we would like to point out some alternative structures in use in the international stem cell research environment. In the UK, the Human Fertilization and Embryology Authority, which regulates hESC research, is required to have a majority of non-scientists on its decision-making committee. In addition, internationally, bodies such as the UK's Human Fertilization and Embryology Authority have strong oversight and enforcement capabilities, which the National Academies-recommended ESCROs will not.

Stricter protection against conflict of interest, broader representation of non-scientists, consistent application of guidelines, and oversight and enforcement mechanisms are needed if stem cell research is to be meaningfully regulated.

Protection of research subjects, including egg providers: Proposition 71 exempts the CIRM from "current or future state legislation" regarding the protection of research subjects. The immense amount of hope being placed in stem cell research, and the pressure for early positive results, suggests the need for particularly strong protection of research subjects. Even more is at stake than the lives of the individual research subjects. The fate of gene therapy research reminds us that any tragedy that results from inappropriate clinical trials would set back stem cell research many years or even decades.

Women who provide eggs for stem cell research will effectively be the first research subjects under the CIRM program. Though the National Academies guidelines acknowledge the serious risks of the hormones used in conjunction with surgical egg extraction, they do not require that women providing eggs be cared for by a physician who is not involved with the research, placing women at risk in situations ripe for conflict of interest.

Volunteers and recruits who provide eggs for research should receive no-cost medical treatment for any condition arising out of the egg extraction process. (The guidelines state that women providing eggs should be informed as to whether or not such coverage is provided, and state that "in general, compensation is not assured.")

Research subjects should also be afforded the protection of being cared for by a physician without conflict of interest, and the cost of any injuries they may sustain should be covered by the researchers or by CIRM.

Implementation of safeguards to prevent misuse of technology for human reproductive cloning and human inheritable genetic modification: We recognize that reproductive cloning is prohibited by Proposition 71 and by California law, but are concerned that mechanisms are needed to maintain control of technologies that will be developed in the service of biomedical advance.

Procedures are needed for tracking and monitoring the derivation, use, and disposal of clonal embryos produced by SCNT, in order to prevent their misappropriation and misuse in efforts to produce cloned or genetically modified human children. The National Academies guidelines include detailed recommendations about procedures for tracking and monitoring the derivation, use, and disposal of cell lines, and these procedures should be extended to clonal embryos.

The modification of the human germline is one of the most profound issues to confront scientists today. Crossing this threshold is likely to change how we think of "human," and is likely to have many profound socioeconomic effects. The genetic modification of stem cells is a key step towards inheritable genetic modification, and must be carefully monitored. Yet the only guidance offered by the National Academies report is, "Further research into genetic modification of hES cells is important." We request that the CIRM Standards Working Group contract to study how other US and international hESC research entities are addressing these issues.

At present there is no mechanism for ensuring that CIRM grantees do not use the expertise gained from use of CIRM funding for future efforts toward applications widely considered unethical. One possibility would be to have each grantee sign a pledge not to conduct or aid others in conducting research on reproductive cloning or IGM.

Patents on human genetic material and "upstream" research: Although the ICOC is looking to a special committee for advice on intellectual property, the language of Proposition 71 asks this working group "to recommend to the ICOC standards for all medical, socioeconomic, and financial aspects of clinical trials and therapy delivery."

Evidence is mounting that patents on human genetic material, human genes, stem cells and stem cell lines inhibit important biomedical research and are interfering with patient care. Intellectual property guidelines for Proposition 71-funded research should be driven by this recognition, as well as by the recognition that publicly funded research should be driven by the public good.

Additionally, standards should be established recognizing that an individual or a group's genetic and biological material differ from other patentable inventions, and should not be privatized or commercialized. They are parts of people, raising individual rights issues about granting companies monopolies over their use, including rights of privacy and reproductive choice, as well as freedom of religion, expression and speech.

ELSI research: Better understanding of the ethical, legal, and social implications (ELSI) of stem cell research among the public, scientific research, political leaders, and social scientists will improve the appropriate development of stem cell research and therapies. We are encouraged that the ICOC has included an ELSI component in the CIRM's first round of training grants, and appears to be receptive to the idea of future funding focusing on ELSI issues. We encourage you to play an important role in advising the ICOC and the grants working group on these matters.

We hope that this outline of some of our concerns helps establish a tone of constructive dialog among us. We look forward to helping you establish robust standards for stem cell research in California, which will surely be a model for elsewhere.

Center for Genetics and Society
Pro-Choice Alliance for Responsible Research